Assessment of the predictive value of plasma proteins in oesophageal adenocarcinoma treatment
Applications are invited for a Tenovus Scotland PhD studentship to start in September 2021. The project will be supervised by Drs Alan Stewart and Swati Arya in the School of Medicine and Dr Sally Shirran in the School of Biology. The studentship is funded for 3 years with a tax-free stipend at UKRI rate. Tuition fees at the Home (UK) rate will also be paid.
There is no provision for “Overseas” students fees; only students that qualify for “Home” fees should apply. Further guidance can be found here: https://www.st-andrews.ac.uk/study/fees-and-funding/postgraduate/
Note that EU students starting their studies in the 2021-2022 academic year, who do not have pre-settled or settled status in the UK, will be considered as “Overseas” for tuition fee purposes. EU students starting their studies in the 2021-2022 academic year who have pre-settled or settled status in the UK, and meet the residency conditions of three years in the UK/EU/EEA/Switzerland, will be considered as “Home” for tuition fee purposes. Students living in the Republic of Ireland will be considered as ‘Home’ for tuition fee purposes.
Oesophageal adenocarcinoma (OAC) is one of the leading causes of cancer mortality worldwide, with a poor 5-year survival rate (less than 15%). The UK has the highest rates of oesophageal cancer in Europe, (National Cancer Registry Report, 2014). It is asymptomatic in early stages and has no biomarkers for its early detection which leads to late diagnosis and poor prognosis resulting in high mortality rate. Incidence is increasing rapidly, with yearly increases of ~4% for females and ~5% for males over the last 20 years. The number of cases in UK is thus predicted to double by 2035, with an accompanying rise in the number of patients seeking treatment.
Curative therapy consists of surgery, either alone or in combination with adjuvant or neo-adjuvant chemotherapy or radiation, or combination chemoradiotherapy regimens (neo-CRT). Multimodal neo-CRT regimens have been shown to increase 5-year survival to 60% in responding patients, compared to chemotherapy alone. However, only a minority of patients respond to this treatment, meaning the majority (70-80%) of patients will experience treatment-related toxicity and delay to surgery with no clinical benefit. There are currently no clinico-pathological means of predicting which patients will benefit from neo-CRT treatment. There is therefore an urgent need to improve OAC disease management and treatment strategies.
The aim of this study is to identify plasma proteins which may be used as markers for prediction of OAC patient response to neo-CRT treatment in a reliable manner. Together with Dr Sally Shirran and the Mass Spectrometry Team at St Andrews, we have standardised a quantitative proteomic technique for analysis of blood plasma, Sequential Window Acquisition of all THeoretical fragment-ion spectra-Mass Spectrometry (SWATH-MS). This technique allows accurate and sensitive quantitative measurement of 1,000s of proteins in a particular sample. This approach can be directly utilised for the proteomic analysis of human plasma from OAC patients undergoing different forms of treatments (supplied by our collaborator, Dr Margaret Dunne, Trinity College Dublin). We will also apply digital learning algorithms that will analyse the large scale quantitative mass spectrometry data in combination with the anonymised clinico-pathological and patient history data to identify subsets of plasma proteins that can be used to predict an individual’s response to treatment and likely disease progression.
The successful candidate will be based in the School of Medicine at the heart of the St Andrews Science Campus at North Haugh. The student will receive training in cellular and molecular techniques. Specifically, methodologies will include sample preparation for mass spectrometry, SWATH-MS analysis, ELISA and bioinformatics and statistics – knowledge of these techniques will position the student well for a career in research after their doctoral studies. The student will also benefit from the University’s GRADskills programme. This is an award-winning transferable skills programme aimed at research postgraduates, which includes courses relating to scientific communication, thesis/research article writing, statistics and intellectual property protection. The student will also have the opportunity to regularly present their work and to attend external scientific meetings.
Arya S, Emri E, Synowsky, SA, Shirran SL, Barzegar-Befroei N, Peto T, Botting CH, Lengyel I, Stewart AJ. (2018) Quantitative analysis of hydroxyapatite-binding plasma proteins in genotyped individuals with late-stage age-related macular degeneration. Experimental Eye Research 172: 21-29.
Arya S, Wiatrek-Moumoulidis D, Synowsky SA, Shirran SL, Botting CH, Powis SJ, and Stewart AJ. (2019) Quantitative analysis of large-scale proteomic changes in LPS-activated monocyte-derived dendritic cells: A SWATH-MS study. Scientific Reports 9: 4343.
Brieu N, Gavriel CG, Nearchou IP, Harrison DJ, Schmidt G, Caie PD (2019) Automated tumour budding quantitation by machine learning augments TNM staging in muscle invasive bladder cancer prognosis. Scientific Reports 9: 5174.
How to Apply
We are looking for enthusiastic candidates who hold a first or upper-second class degree (and/or MSc) in Biochemistry, Chemistry (Analytical) or a related subject from a recognised academic institution. Applicants with an interest in mass spectrometry, bioinformatics and/or statistics are particularly encouraged to apply. To apply, please visit the University of St Andrews website and download the PhD application form. Full details on how to apply are given here: http://www.st-andrews.ac.uk/study/pg/apply/research/.
Informal enquiries can be addressed to Dr Alan Stewart (E-mail: firstname.lastname@example.org).
Closing Date: 14th May 2021